Obesity is a major risk factor for developing type 2 diabetes mellitus (T2DM). Oxyntomodulin (OXM), a 37-amino acid peptide hormone derived from proglucagon, is an attractive potential therapy for treatment of T2DM due to its multifaceted effects on glucose homeostasis, food intake and energy expenditure. Remarkably, the weight loss and glucose lowering effects of OXM were found to be superior to those of the glucagon-like peptide-1 (GLP-1) receptor only agonists after infusion in preclinical models. However, the clinical application of OXM is limited by its short circulatory half-life; hence, PEG and lipid modified OXM analogs have been explored. While these conjugates have shown significantly longer circulatory half-lives, they often exhibit considerably reduced potency; as a result, relatively large quantities of the modified peptides are injected during their administration. These large doses have limited the exploration of alternative delivery technologies such as microneedles or nanoparticles.